Pharmacokinetics of acute tryptophan depletion using a gelatin-based protein in male and female Wistar rats.

The essential amino acid tryptophan is the precursor of the neurotransmitter serotonin. By depleting the body of tryptophan, brain tryptophan and serotonin levels are temporarily reduced. In this paper, several experiments are described in which dose and treatment effects of acute tryptophan depletion (ATD) using a gelatin-based protein-carbohydrate mixture were studied in male and female Wistar rats. Two or three doses of tryptophan depleting mixture resulted in 65-70% depletion after 2-4 h in males. ATD effects were similar in females, although females may return to baseline levels faster. Treatment effects after four consecutive days of ATD were similar to the effects of 1 day of treatment. Object recognition memory was impaired 2, 4, and 6 h after the first of two doses of ATD, suggesting that the central effects occurred rapidly and continued at least 6 h, in spite of decreasing treatment effects on plasma tryptophan levels at that time point. The method of acute tryptophan depletion described here can be used to study the relationship between serotonin and behaviour in both male and female rats.

Influence of sex and estrous cycle on the effects of acute tryptophan depletion induced by a gelatin-based mixture in adult Wistar rats.

Women are more vulnerable to develop depression and anxiety disorders than men. This may be related to higher serotonergic vulnerability in women. Serotonergic vulnerability entails that differences between people in the regulation of serotonin (5-HT) determine the vulnerability of an individual to develop depression or other 5-HT-related disorders. The aim of the present experiment was to evaluate whether male and female Wistar rats differ in serotonergic vulnerability. Here, a stronger behavioral response to acute tryptophan (TRP) depletion was assumed to reflect serotonergic vulnerability. Twenty-four male and 48 female rats were repeatedly subjected to treatment with a gelatin-based protein-carbohydrate mixture, either with or without L-tryptophan. Female estrous cycle phase was determined by means of vaginal smears and the females were divided into two groups based on their estrous cycle phase: pro-estrus/estrus and met-estrus/di-estrus. Blood samples showed stronger TRP depletion in males than females. There was no effect of estrous cycle on plasma TRP concentrations. In contrast, treatment effects on some brain TRP concentrations were influenced by estrous cycle phase, females in pro-estrus/estrus showed the strongest response to TRP depletion. In the open field test and home cage emergence test, females in pro-estrus/estrus also showed the strongest behavioral response to acute TRP depletion. In general, females showed more activity than males in anxiety-related situations and this effect appeared to be enhanced by TRP depletion. In the social interaction test, passive body contact in males and females in pro-estrus/estrus was decreased after TRP depletion whereas it was increased in females in the met-estrus/di-estrus phase. Acute TRP depletion affected object recognition, but did not affect behavior in the forced swimming test and a reaction time task. It is concluded that sex and estrous cycle phase can influence the behavioral response to TRP depletion, and that females in pro-estrus/estrus show the strongest behavioral response to acute TRP depletion.

Acute tryptophan and serotonin depletion using an optimized tryptophan-free protein-carbohydrate mixture in the adult rat.

In contrast to humans, a tryptophan (TRP)-free amino acid (AA) mixture only leads to moderate depletion in plasma TRP levels in adult rats. In this study we evaluated the effects of an acute administration of a TRP-free protein-carbohydrate nutritional mixture in adult male Wistar rats. Plasma amino acid levels were examined at 2 and 4h starting after the first administration. Furthermore, the concentrations of amino acid, serotonin (5-HT), dopamine (DA) and their metabolite (5-hydroxyindolacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC), respectively) were measured within the striatum, hippocampus and cortex. In the TRP depleted animals, the TRP/sigmaLNAA ratio (LNAA: large neutral amino acids) was substantial decreased at 2 and 4h after the first administration of the oral administration (by 71 and 78%, respectively). Four hours after treatment central TRP and 5-HT concentrations were decreased by 50%. Both peripheral and central TRP levels returned to basal values in the group treated with the nutritional mixture supplemented with TRP. Surprisingly, tyrosine levels were also reduced after oral administration of the protein-carbohydrate mixture without affecting central DA concentrations. In conclusion, the TRP-free protein-carbohydrate nutritional mixture appears to be an efficient tool to substantially reduce plasma and central TRP levels in adult rat.